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Recent Progress of Molecular Mechanism of Gene Expression

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 April 2019) | Viewed by 26421

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Special Issue Editor

Dr. Yasufumi Murakami

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Guest Editor

Department of Biological Science and Technology, Tokyo University of Science, Tokyo, Japan
Interests: epigenetics; non-coding RNA; genome-wide analysis of gene expression; chromatin remodeling; bookmarking mechanism of gene expression

Special Issue Information

Dear Colleagues,

The purpose of this Special Issue is to update our knowledge of the molecular mechanisms of gene expression. Since completion of the human genome analysis, various omics approaches have been tried, and an enormous amount of data has been produced. The discovery of non-coding RNAs and their regulatory function in intracellular and intercellular phenomena is a big issue. Currently, various bio-informatics research tools for molecular biology have been developed, and the efficiency of molecular biology research has been further improved. Although our knowledge of the mechanisms of gene expression has been greatly advanced, we need to update on various cutting-edge research findings in order to reach an integrated view of the gene expression mechanisms identified up to this point. Epigenetic analysis, the analysis of gene expression in a genome-wide manner, the role of various non-coding RNAs (including their regulatory mechanisms of expression), the bookmarking mechanism of gene expression are all important issues to consider for assembling a global picture of gene expression. I would like to encourage colleagues to submit manuscripts dealing with the subjects mentioned above. It would be nice if you could discuss the biological significance of the molecular mechanisms presented in your manuscript. Discussion of future applications of the novel mechanisms described in your manuscript will strengthen your paper. Manuscripts on bio-informatics are also suitable for this Special Issue if they are related to gene expression. I hope that this collection of high-quality papers will help us to achieve an integrated understanding of gene expression.

Dr. Yasufumi Murakami
Guest Editor

Manuscript Submission Information

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Keywords

epigenetic analysis
analysis of gene expression in a genome-wide manner
role of various non-coding RNAs
bookmarking mechnism in gene expression
gene expression network
novel research tools for the analysis of gene expression
bio-informatics

Published Papers (6 papers)

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Research

17 pages, 3655 KiB

Open AccessArticle

Genome-Wide Identification, Expression Analysis, and Subcellular Localization of Carthamus tinctorius bHLH Transcription Factors

by Yingqi Hong, Naveed Ahmad, Yuanyuan Tian, Jianyu Liu, Liyan Wang, Gang Wang, Xiuming Liu, Yuanyuan Dong, Fawei Wang, Weican Liu, Xiaowei Li, Xu Zhao, Na Yao and Haiyan Li

Int. J. Mol. Sci. 2019, 20(12), 3044; https://doi.org/10.3390/ijms20123044 - 21 Jun 2019

Cited by 32 | Viewed by 4359

Abstract

The basic helix–loop–helix (bHLH) family is the second largest superfamily of transcription factors that belongs to all three eukaryotic kingdoms. The key function of this superfamily is the regulation of growth and developmental mechanisms in plants. However, the bHLH gene family in Carthamus tinctorius has not yet been studied. Here, we identified 41 bHLH genes in Carthamus tinctorius that were classified into 23 subgroups. Further, we conducted a phylogenetic analysis and identified 10 conserved protein motifs found in the safflower bHLH family. We comprehensively analyzed a group of bHLH genes that could be associated with flavonoid biosynthesis in safflower by gene expression analysis, gene ontology annotation, protein interaction network prediction, subcellular localization of the candidate CtbHLH40 gene, and real-time quantitative expression analysis. This study provides genome-wide identification of the genes related to biochemical and physiological processes in safflower. Full article

(This article belongs to the Special Issue Recent Progress of Molecular Mechanism of Gene Expression)

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14 pages, 1109 KiB

Open AccessArticle

CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions

by Marta del Pino, Adriana Sierra, Lorena Marimon, Cristina Martí Delgado, Adriano Rodriguez-Trujillo, Esther Barnadas, Adela Saco, Aureli Torné and Jaume Ordi

Int. J. Mol. Sci. 2019, 20(9), 2262; https://doi.org/10.3390/ijms20092262 - 7 May 2019

Cited by 29 | Viewed by 3075

Abstract

Background: Squamous intraepithelial lesions/cervical intraepithelial neoplasias (SIL/CIN) are high-risk human papilloma virus (hrHPV)-related lesions which are considered as high grade (HSIL/CIN2-3) or low grade (LSIL/CIN1) lesions according to their risk of progression to cervical cancer (CC). Most HSIL/CIN2-3 are considered as transforming hrHPV infections, so truly CC precursors, although some clear spontaneously. hrHPV testing has a high sensitivity for the detection of HSIL/CIN2-3 but a relatively low specificity for identifying transforming lesions. We aimed to determine whether the combination of CADM1, MAL and miR124 promoter methylation status assessed in histological samples can be used as a biomarker in the identification of transforming HSIL/CIN lesions. Design: 131 cervical biopsies, including 8 cases with no lesion and a negative hrHPV test result (control group), 19 low-grade (L)SIL/CIN1, 30 HSIL/CIN2, 60 HSIL/CIN3, and 14 CC were prospectively collected. hrHPV was detected and genotyped using the polymerase chain reaction (PCR)-based technique SPF10 HPV LIPA. A multiplex quantitative methylation-specific PCR (qMSP) was used to identify the methylation status of the CADM1, MAL, and miR124 promoter genes. Results: Significantly higher methylation levels of CADM1, MAL and miR-124 were found in HSIL/CIN2-3 and CC compared with normal and LSIL lesions. DNA methylation of at least one gene was detected in 12.5% (1/8) of normal samples, 31.5% (6/19) of LSIL/CIN1, 83.3% (25/30) of HSIL/CIN2, 81.6% (49/60) of HSIL/CIN3 and 100% (14/14) of CC (p < 0.001). The sensitivity and specificity for HSIL/CIN2-3 and CC of having at least one methylated gene were 84.6% and 74.0%, respectively. The sensitivity and specificity of the combination of at least one methylated gene and a positive hrHPV test were 80.7% and 85.1% for HSIL/CIN2-3 and CC, respectively. Conclusions: The methylation rate of CADM1, MAL and miR124 increases with the severity of the lesion. Further research is warranted to evaluate the usefulness of these biomarkers for the identification of transforming HSIL/CIN. Full article

(This article belongs to the Special Issue Recent Progress of Molecular Mechanism of Gene Expression)

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17 pages, 2816 KiB

Open AccessArticle

YY1/BCCIP Coordinately Regulates P53-Responsive Element (p53RE)-Mediated Transactivation of p21^Waf1/Cip1

by Yi Sui, Tingting Wu, Fuqiang Li, Fei Wang, Yong Cai and Jingji Jin

Int. J. Mol. Sci. 2019, 20(9), 2095; https://doi.org/10.3390/ijms20092095 - 28 Apr 2019

Cited by 12 | Viewed by 4395

Abstract

Transactivation of p21 (cyclin-dependent kinase inhibitor 1A, CDKN1A) is closely related to the recruitment of transcription cofactors at the p53 responsive elements (p53REs) in its promoter region. Human chromatin remodeling enzyme INO80 can be recruited to the p53REs of p21 promoter and negatively regulates p21. As one of the key subunits of the INO80 complex, YY1 has also been confirmed to bind to the p53RE sites of p21 promoter. Importantly, YY1 was recently reported to be bound and stabilized by BCCIP (BRCA2 and CDKN1A-interacting protein). Therefore, we hypothesized that the YY1/BCCIP complex plays an important role in regulating the transactivation of p21. Here we present evidence that the YY1/BCCIP complex coordinatively regulates p53RE-mediated p21 transactivation. We first confirmed the cross-interaction between YY1, BCCIP, and p53, suggesting an intrinsic link between three proteins in the regulation of p21 transcription. In dual luciferase assays, YY1 inhibited p53RE-mediated luciferase activity, whereas BCCIP revealed the opposite effect. More interestingly, the region 146–270 amino acids of YY1, which bound to BCCIP, increased p53-mediated luciferase activity, indicating the complexity of the YY1/BCCIP complex in co-regulating p21 transcription. Further in-depth research confirmed the co-occupancy of YY1/BCCIP with p53 at the p53RE-proximal region of p21. Lentiviral-mediated knockdown of BCCIP inhibited the recruitment of p53 and YY1 at the p53RE proximal region of p21; however, this phenomenon was reversed by expressing exogenous YY1, suggesting the collaborative regulation of YY1/BCCIP complex in p53RE-mediated p21 transcription. These data provide new insights into the transcriptional regulation of p21 by the YY1/BCCIP complex. Full article

(This article belongs to the Special Issue Recent Progress of Molecular Mechanism of Gene Expression)

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46 pages, 13245 KiB

Open AccessArticle

Regulation Mechanism of MYC Family Transcription Factors in Jasmonic Acid Signalling Pathway on Taxol Biosynthesis

by Yunpeng Cui, Rongjia Mao, Jing Chen and Zhigang Guo

Int. J. Mol. Sci. 2019, 20(8), 1843; https://doi.org/10.3390/ijms20081843 - 14 Apr 2019

Cited by 18 | Viewed by 5891

Abstract

Paclitaxel is an important anticancer drug. The phytohormone jasmonic acid can significantly induce the biosynthesis of paclitaxel in Taxus, but the molecular mechanism has not yet been resolved. To establish the jasmonic acid signalling pathway of Taxus media, based on the gene of the jasmonic acid signalling pathway of Arabidopsis thaliana, sequence analysis was performed to isolate the jasmonic acid signal from the transcriptome, a transcriptional cluster of pathway gene homologs and the full length of 22 genes were obtained by RACE PCR at 5′ and 3′: two EI ubiquitin ligase genes, COI1-1 and COI1-2;7 MYC bHLH type transcription factor (MYC2, MYC3, MYC4, JAM1, JAM2, EGL3, TT8); 12 JAZ genes containing the ZIM domain; and MED25, one of the components of the transcriptional complex. The protein interaction between each were confirmed by yeast two hybridization and bimolecular fluorescence complementation based on similar genes interaction in Arabidopsis. A similar jasmonate signaling pathway was illustrated in T. media. All known paclitaxel biosynthesis genes promoters were isolated by genome walker PCR. To investigate the jasmonate signaling effect on these genes’ expression, the transcription activity of MYC2, MYC3 and MYC4 on these promoters were examined. There are 12, 10 and 11 paclitaxel biosynthesis genes promoters that could be activated by MYC2, MYC3 and MYC4. Full article

(This article belongs to the Special Issue Recent Progress of Molecular Mechanism of Gene Expression)

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22 pages, 6460 KiB

Open AccessArticle

SIRT2 Inhibition Results in Meiotic Arrest, Mitochondrial Dysfunction, and Disturbance of Redox Homeostasis during Bovine Oocyte Maturation

by Dejun Xu, Lin Wu, Xiaohan Jiang, Li Yang, Jianyong Cheng, Huali Chen, Rongmao Hua, Guoxia Geng, Lulu Yang and Qingwang Li

Int. J. Mol. Sci. 2019, 20(6), 1365; https://doi.org/10.3390/ijms20061365 - 18 Mar 2019

Cited by 26 | Viewed by 4819

Abstract

SIRT2, a member of the sirtuin family, has been recently shown to exert important effects on mitosis and/or metabolism. However, its roles in oocyte maturation have not been fully clarified. In this study, SIRT2, located in the cytoplasm and nucleus, was found in abundance in the meiotic stage, and its expression gradually decreased until the blastocyst stage. Treatment with SIRT2 inhibitors resulted in the prevention of oocyte maturation and the formation of poor-quality oocytes. By performing confocal scanning and quantitative analysis, the results showed that SIRT2 inhibition induced prominent defects in spindle/chromosome morphology, and led to the hyperacetylation of α-tubulin and H4K16. In particular, SIRT2 inhibition impeded cytoplasmic maturation by disturbing the normal distribution of cortical granules, endoplasmic reticulum, and mitochondria during oocyte meiosis. Meanwhile, exposure to SirReal2 led to elevated intracellular reactive oxygen species (ROS) accumulation, low ATP production, and reduced mitochondrial membrane potential in oocytes. Further analysis revealed that SIRT2 inhibition modulated mitochondrial biogenesis and dynamics via the downregulation of TFAM and Mfn2, and the upregulation of DRP1. Mechanistically, SIRT2 inhibition blocked the nuclear translocation of FoxO3a by increasing FoxO3a acetylation, thereby downregulating the expression of FoxO3a-dependent antioxidant genes SOD2 and Cat. These results provide insights into the potential mechanisms by which SIRT2-dependent deacetylation activity exerts its effects on oocyte quality. Full article

(This article belongs to the Special Issue Recent Progress of Molecular Mechanism of Gene Expression)

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13 pages, 2905 KiB

Open AccessArticle

p21^WAF1/Cip1 Regulation by hYSK1 Activates SP-1 Transcription Factor and Increases MMP-2 Expression under Hypoxic Conditions

by Mee-Hyun Lee, Joydeb Kumar Kundu and Bu Young Choi

Int. J. Mol. Sci. 2019, 20(2), 310; https://doi.org/10.3390/ijms20020310 - 14 Jan 2019

Cited by 2 | Viewed by 3426

Abstract

The hYSK1, a serine/threonine kinase (STK)-25, has been implicated in a variety of cellular functions including cell migration and polarity. We have recently reported that hYSK1 down-regulated the expression and functions of p16^INK4a, a cell cycle regulatory protein, thereby enhancing migration and growth of cancer cells under hypoxic conditions. In this study, we further investigated the mechanisms underlying downregulation of p16^INK4a and anti-migratory function of hYSK1. Our study revealed that p21^WAF1/Cip1 is a novel binding partner of hYSK1. Moreover, the interaction between hYSK1 and p21^WAF1/Cip1 led to the inhibition of SP-1 transcriptional activity, as revealed by a significant down-regulation of SP-1-mediated transactivation of p16^INK4a promoter, and accelerated MMP-2 expression. Conversely, the knock-down of hYSK1 enhanced the p16^INK4a promoter activity and protein expression, and diminished MMP-2 transcription and protein levels in hypoxic conditions as compared to control. Taken together, hYSK1 blocks the p21^WAF1/Cip1 functions by direct interaction and inhibits the p16^INK4a expression and induces MMP-2 expression by its regulations of SP-1 transcriptional activity under the hypoxia conditions. Full article

(This article belongs to the Special Issue Recent Progress of Molecular Mechanism of Gene Expression)

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